Overcoming treatment resistance in glioblastoma multiforme by tumour specific inhibition of DNA repair.

Brain tumour patients currently survive an average of just one year because their cancers resist treatment. This project aims to change that by making radiotherapy and chemotherapy far more effective against glioblastoma multiforme, the most common and aggressive malignant brain tumour, while leaving healthy tissue unharmed. The problem is that tumour cells repair the DNA damage that radiation and chemotherapy inflict, so the treatments fail. The researchers have already had promising results with drugs called PARP inhibitors, which block this repair process. They will now run a clinical trial to see which patients actually benefit, and why. They will also test whether PARP inhibitors help radiotherapy kill the stem-like cells that likely cause most tumour recurrences. If PARP inhibitors fall short, the team will test alternative drugs that alter how cells respond to radiation. Finally, they will investigate a new approach for a chemotherapy-resistant brain tumour type: a drug that reduces levels of a protein called MGMT, which normally shields tumour cells from chemotherapy. If this succeeds, the immediate impact is straightforward: longer survival and better quality of life for brain tumour patients, without the severe side effects that come from hitting healthy tissues. This is applied, patient-focused research with a clear clinical endpoint.